Project Summary/Abstract The accuracy and precision of saccades are important to vision. Our long term goal is to identify the neural mechanisms that underlie saccade motor control. As with other movements, the cerebellum plays a key role in fine tuning saccadic eye movements. Specifically, intact oculomotor vermis (OMV) and caudal fastigial nucleus (cFN) is critical for producing accurate saccades. Much of our understanding of the physiology of neurons in the cFN and Purkinje (P-) cells in the OMV during saccades has relied on saccades made to single targets that appear in the visual periphery. In such a visually guided saccade task, the vectors of the retinotopic target and the saccade motor command are congruent. However, in real life, saccades often must be coordinated with other saccades or other types of eye movement that intervene between the programming and execution of a saccade. Such interruptions dissociate the vector of the saccade to be executed from its retinotopic target vector. The brain must update the vector of the upcoming saccade by combining the retinotopic target vector with information about the intervening movement. Oculomotor areas of cerebral cortex account only partially for the spatial updating of saccades, implying significant contribution from subcortical structures. We hypothesize that the OMV and the cFN to which it projects play critical roles in this process. These structures receive motor command feedback from brainstem saccade premotor neurons. The feedback signal could be used to adjust the motor command of the final saccade during spatial updating via cFN projection to saccade premotor neurons. We will test this hypothesis in a monkey performing a double-step saccade task (DST). In this task, the monkey makes two sequential saccades in the dark to previously flashed visual targets. The task requires the brain to combine the motor command of the first saccade with the retinotopic location of the flashed second target to produce an accurate second saccade. Specifics Aims 1 and 2 examine the activity of neurons in the cFN and OMV P-cells during spatial updating of saccades. We will test the hypothesis that by combining the retinotopic target signal in the SC with the feedback motor command of the first saccade of a DST, the cerebellum computes a corrective signal. This corrective signal is represented in the saccade-related activity of the neurons. Specific Aim 3 perturbs the processing of spatial updating of saccades before the second saccade is launched. We will briefly increase P-cell activity by using optogenetic activation triggered by the first saccade, and examine the effects on the second saccades. Overall Impact: The cerebellum plays an important role in the accuracy, precision, and temporal sequencing of movements. We will study the cerebellum?s contribution to the coordination of a sequence of saccades?well understood movements that provide a platform for understanding motor coordination more generally. The results of our studies will improve our understanding of the neural basis of motor coordination and will guide the development of behavioral strategies to rehabilitate patients with cerebellar diseases.